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Lloyd E King

Publications and source records attributed to Lloyd E King.

At least 19 recordsLinked to original sources
PubMed2006

Oestrogen receptor-beta expression in melanocytic lesions.

Melanomas rarely occur before puberty, have a higher death rate for males, and tend to be more invasive during pregnancy. Prior to the discovery of a second oestrogen receptor (ERbeta), studies with the initial oestrogen receptor, ERalpha, showed no obvious role for oestrogen in the pathophysiology of benign or malignant melanocytic lesions. To investigate the specific immunostaining patterns of ERalpha and ERbeta, benign nevocytic nevi, dysplastic nevi with mild, moderate and severe cytological atypia, lentigo malignas and melanomas of varying depth (Clark) and thickness (Breslow) were studied. ERbeta but not ERalpha was the predominant oestrogen receptor we found in all types of benign and malignant melanocytic lesions. The most intense ERbeta immunostaining was seen in melanocytes in dysplastic nevi with severe cytological atypia and in lentigo malignas. ERbeta expression levels also correlated with the malignant tumor microenvironment; i.e., melanocytes in proximity with keratinocytes>deeper dermal melanocytes in contact with stroma>minimally invasive melanomas>Clark Level III/IV or thick melanomas (Breslow). Discovery that ERbeta expression varies in relation to the tumor microenvironment and increasing depth of invasion suggests its possible usefulness as a surrogate marker for neoplasia and prognosis in malignant melanoma.

Biomarkers, Tumor↗
PubMed2004

A protective role for matrix metalloproteinase-3 in squamous cell carcinoma.

Elevated expression of matrix metalloproteinase-3 (MMP-3/stromelysin-1) is associated with a variety of tumor types, although its in vivo functional role remains unclear. In human and murine squamous cell carcinoma (SCC), MMP-3 is expressed in the stromal compartment at all of the stages of tumor progression and is expressed by the malignant epithelial cells in late-stage, highly invasive tumors. To elucidate whether MMP-3 plays a causal role during SCC, wild-type and MMP-3 null mice were subjected to chemical carcinogenesis procedures by topical application of either the complete carcinogen 1-methyl-3-nitro-1-nitroso-guanidine or two-stage initiation and promotion with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Contrasting with our expectations, tumors originating on MMP-3 null mice had enhanced initial tumor growth rates as compared with control animals, although there was no difference in tumor onset or incidence. This elevated rate in growth was coupled with an elevated proliferative index and a reduced vasculature density but with no significant effect on apoptosis. Tumors from MMP-3 null mice had a prevalence of undifferentiated spindle tumors as compared with controls, which was concomitant with a higher percentage of MMP-3 null mice evidencing surface lung metastases. Tumor progression in MMP-3 null mice was inversely associated with leukocyte infiltration, in which an overall reduction in tumor-associated macrophages and neutrophils was evident. We propose that MMP-3 is expressed as a protective response and plays an important role in host defense during SCC tumorigenesis.

Animals↗
PubMed2004

Adult-onset Alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model.

Alopecia areata (AA) is an autoimmune disease that targets actively growing (anagen) hair follicles in humans and other mammals. C3H/HeJ, but not C57BL/6J, mice spontaneously develop an adult-onset form of AA. A segregating population of C3HB6F2 female mice (n=1096), generated from crossing these two strains, was used for genome-wide linkage analysis to identify AA genetic susceptibility. Previous analysis identified susceptibility intervals on chromosomes 17 (Alaa1) and 9 (Alaa2). Using additional markers in these intervals and saturation mapping purported intervals on chromosomes 8 and 15, two additional regions were identified (Alaa3 and Alaa4, respectively). Human gene association studies identified specific human leukocyte antigen intervals comparable with those (major histocompatibility complex) found in Alaa1 in the mouse. Other human studies identified genes not found in this linkage study, but these human transcription factors are directly regulated by genes within Alaa1. These results indicate the necessity of integrating both gene association and genome-wide linkage studies in both mice and humans to understand the complex nature of these and other polygenic diseases.

Age of Onset↗
PubMed2004

Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation.

Retinoic acid has long been known to alter skin and hair growth but an exact mechanism is unclear. This study was performed to examine the sites of endogenous retinoic acid synthesis in the cycling hair follicle to better understand the role retinoic acid plays in this process. Retinal dehydrogenases (Aldh1a1, 2, and 3, formerly Raldh 1, 2, and 3) are the enzymes responsible for the last step in retinoic acid synthesis. Immunohistochemistry was performed on adult C57BL/6J mouse skin sections with antibodies against Aldh1a2 and Aldh1a3. Aldh1a2 expression was seen primarily in the outer root sheath and basal/spinous layer during all stages of the hair cycle, and in the bulge during anagen and early catagen, whereas Aldh1a3 expression was primarily in the dermal papilla, pre-cortex, and hair shaft during mid-late anagen. The expression patterns of these two similar retinoic acid synthesizing enzymes at specific follicular sites suggest that they mediate and are regulated by different epithelial proliferation and differentiation signaling pathways.

Aldehyde Oxidoreductases↗
PubMed2004

Alpha 2-HS glycoprotein (fetuin-A) modulates murine skin tumorigenesis.

Fetuin, a major serum glycoprotein secreted by the liver, has been shown to play a role in bone development, calcium homeostasis and insulin sensitivity. In an earlier study, we demonstrated that bovine fetuin can bind to the plasma membrane of squamous and spindle-cell carcinoma cells. To test our hypothesis that fetuin plays a causal role in skin tumorigenesis, fetuin-A null and wild-type mice were challenged using a two-stage chemically-induced carcinogenesis protocol with DMBA (7,12-dimethylbenzo(a)anthracene) as the initiator, followed by twice weekly treatments with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). Tumors that developed on fetuin-A null animals grew at a similar rate as those arising on their wild-type counterparts. Absence of fetuin-A did not alter tumor onset or conversion to squamous cell carcinoma, but reduced the number of tumors per mouse by 30%. This correlated with a decrease in tumor burden in fetuin-A null animals compared to wild-type weeks 18-22 from tumor onset. In addition, tumors arising on fetuin-A null mice had a diminished proliferative index with no change in cell survival or neovascularization in comparison with wild-type tumors. Our results suggest that fetuin-A contributes to early stages of skin tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

Mouse alopecia areata models: an array of data on mechanisms and genetics.

Laboratory mice have become the premier animal model for most human and domestic animal diseases, and they have long been the model of choice for studying mammalian genetics, especially since the advent of genetic engineering. Many remarkable discoveries have been made through intense study of these wonderful small mammals, and undoubtably many more will be made. It is no surprise that one mouse model for alopecia areata (AA) has been found possibly many more will be, some of which exhibit rare phenotypes found in subpopulations of humans with the disease, such as nail deformities, thyroid disease, inflammatory bowel disease, and autoimmune polyendocrine syndrome type 1. Intense investigation by many groups into the first model, the adult onset form of AA (using the C3H/HeJ inbred strain), found similarities as well as differences with commonly held ideas concerning human AA. Regardless of some of the controversies, much insight has been gained from studying these and other rodent and domestic animal models which has opened up new ideas and discussions of AA and its treatment.

Alopecia Areata↗
PubMed2003

Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice.

Alopecia areata is an autoimmune disease that targets actively growing (anagen) hair follicles in humans, mice, rats, dogs, horses, and cattle. C3H/HeJ mice spontaneously develop alopecia areata from 5 mo of age and older in females and later in males. Frequency of disease approached 20% in a colony by 18 mo of age. C57BL/6J mice do not develop alopecia areata. A segregating F2 population of female mice (n=1096) was generated from crossing these two strains. Alopecia areata (n=138) and clinically normal (n=214) mice were genotyped at 12 mo of age using 211 microsatellite probes. The peak logarithm of odds ratio score on mouse chromosome 17 (10.9) was around marker D17Mit134 at 16.9 cM from the centromere. The mouse histocompatibility locus, H2, the mouse equivalent of human leukocyte antigen in humans, was a likely candidate. Twelve-month-old C3H.SW-H2b/SnJ mice (C3H/HeJ congenic mice in which the H2k purported susceptibility locus was replaced with the H2b purported resistance locus) did not develop alopecia areata, supporting this locus as being important in alopecia areata. A suggestive linkage was also found on mouse Chromosome 9 (logarithm of odds ratio score 2.0) around D9Mit206, 20 cM from the centromere. The interval on mouse Chromosome 17 contains several orthologous genes potentially associated with human alopecia areata.

Alopecia Areata↗
PubMed2003

Culture and immunohistochemical evidence of Chlamydia pneumoniae infection in ulcerative pyoderma gangrenosum.

A potentially contributing factor to the development and chronicity of pyoderma gangrenosum is infection with the relatively recently characterized human pathogen, Chlamydia pneumoniae. C pneumoniae is an obligate intracellular bacterium that can infect endothelial, monocyte, and smooth muscle cells and is associated with cardiopulmonary diseases. A case of serologically, polymerase chain reaction-positive, immunohistochemically, and culture-documented viable C pneumoniae organisms in a chronic pyoderma gangrenosum ulcer is reported, a finding that has not been described previously.

Adult↗
PubMed2003

Crohn's disease of the penis masquerading as pyoderma gangrenosum: a case report and review of the literature.

Both pyoderma gangrenosum (PG) and cutaneous (metastatic) Crohn's disease (CCD) may occur in the setting of inflammatory bowel disease (IBD). Clinical distinction between PG and CCD may be difficult because clinical and pathologic features often are similar. Although surgical debridement is therapeutic in CCD, it may lead to increased tissue loss and disease progression (pathergy) in PG. Thus, it is important to determine a definitive diagnosis before surgical debridement, especially in tissue-sensitive sites. We present a patient with chronic ulceration of the penis who ultimately was diagnosed with CCD following an initial misdiagnosis of PG.

Crohn Disease↗
PubMed2002

Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans.

Alopecia areata is a suspected autoimmune hair loss disease. In a rodent model, alopecia areata can be induced in normal haired C3H/HeJ mice by transfer of skin grafts from mice with spontaneous alopecia areata. At weeks 2, 4, 6, and 10 after surgery, grafted mice were euthanized, skin collected and processed for histology, and RNA extracted. Age-matched sham-grafted mice, and mice with and without spontaneous alopecia areata, were similarly processed. For comparison, skin biopsies from alopecia areata and androgenetic alopecia affected humans were also collected. Skin mRNA processed to cDNA was analyzed using Affymetrix mouse 11K and human 6800 gene chip(R) array technology. Microarray results indicated 42 known genes upregulated or downregulated during onset of mouse alopecia areata consistent with an inflammatory cell-mediated disease pathogenesis involving antigen presentation, costimulation, and a T helper 1 lymphocyte response. In contrast, 114 genes, many regulating immunoglobulin response, were altered late in disease development. In alopecia areata affected humans, 95 genes were significantly modulated. As confirmation of microarray analysis results, lymph node and spleen cells from alopecia areata affected mice injected into normal haired littermates transferred the alopecia areata phenotype. Alopecia areata onset could be inhibited in skin-grafted mice by modulation with B7.1- and B7.2-specific monoclonal antibodies. In addition, depletion of CD4+ CD8+ expressing cells in chronic alopecia areata affected mice using monoclonal antibodies permitted hair regrowth. The results consistently demonstrated the importance of an immune cell-mediated disease mechanism in alopecia areata pathogenesis and suggested targeting antigen-presenting cells and reactive lymphocytes may be effective in alopecia areata treatment.

Adoptive Transfer↗
PubMed2002

Graftskin treatment of difficult to heal diabetic foot ulcers: one center's experience.

BACKGROUND: Chronic diabetes-related foot ulcers result from predisposition, tissue injury, and inadequate reparative mechanisms. Standard care for diabetes-related foot ulcers includes weight off-loading, pressure-relieving footwear, aggressive surgical debridement, and frequent dressing changes. Graftskin is a recently developed living skin construct. OBJECTIVE: To compare Graftskin and standardized wound care to standardized wound care alone in the treatment of difficult to heal diabetes-related neuropathic foot ulcers, and to assess the handling and application characteristics of Graftskin. METHODS: A university dermatology clinic was part of a 24-center prospective, randomized, controlled, parallel group comparative trial of Graftskin for the treatment of difficult to heal neuropathic diabetes-related foot ulcers. Patients were randomly assigned to treatment with Graftskin with aggressive debridement and standardized wound care, or aggressive debridement and standardized wound care alone. Blinding was not feasible due to device visibility during application. RESULTS: Five of nine patients (56%) treated with Graftskin therapy had complete healing. Three of eight control patients (37%) had complete healing. CONCLUSION: Graftskin as an adjunct to aggressive debridement and standardized wound care appears to be a valuable treatment adjunct in patients with difficult to heal diabetes-related neuropathic foot ulcers. The application learning curve was steep and the ease of application exceptional.

Adult↗
PubMed2002

Basal cell carcinoma in young women: an evaluation of the association of tanning bed use and smoking.

Basal cell carcinomas (BCCs) typically occur in middle-aged to elderly patients but less commonly in younger ones. In our experience, most BCCs seen in patients younger than 40 years are found in women. We evaluated 30 women with biopsy-proven BCC and 30 control patients matched for sex, age, and skin type to determine potential risk factors for this population. Tanning bed visits, pack-years of cigarette smoking, recreational sun exposure, number of blistering sunburns, and use of sunscreens were determined for both groups. Among patients with a BCC, the histologic type of tumor, site of involvement, method of treatment, follow-up period, incidence of recurrence, and presence of actinic keratoses were also evaluated. Patients with a BCC had a statistically greater number of pack years of smoking (P =.045), and a greater percentage of these women had experienced blistering sunburns (P =.028). Although women with a BCC had, on average, almost twice as many tanning salon visits (152.2 vs 83.1), this was not statistically significant. Sunscreen use and amount of recreational ultraviolet light exposure were essentially equal between the two groups. Young women with a BCC are more likely to have a past or current history of cigarette smoking and blistering sunburns. Repeated exposure to tanning beds may also be a contributory factor.

Adolescent↗
PubMed2002

Familial ulcerative pyoderma gangrenosum: a report of 2 kindred.

Pyoderma gangrenosum is a rare, chronic ulcerative skin disease. It is a diagnosis of exclusion, after ruling out other causes of cutaneous ulceration. The etiology of pyoderma gangrenosum is poorly understood but is likely multifactorial. We describe 2 families affected by ulcerative pyoderma gangrenosum. This familial clustering suggests a possible genetic role in the development of pyoderma gangrenosum in some cases.

Adult↗